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EDITORIAL
EDITORIAL
Impact of metabolic syndrome on arterial elasticity
JORGE LERMANMTSAC, 1
According to the definition in the Diccionario de la Lengua de la Real Academia Española, a syndrome is “a
group of symptoms that characterize a disease”, and a
disease is “a more or less severe impairment of health”.
Therefore, if we stick to the rigor of definitions, what
we understand by “metabolic syndrome” (MS) today
does not comply accurately with that definition. The
concept we have about this condition is that it is a set
of physical, clinical, and laboratory signs which do not
“characterize a disease”, but which have the capacity
to anticipate –with high predictive value– the further
development of cardiometabolic complications (diabetes and atherosclerosis at different locations). That is
to say that the medical jargon (as in other cases) has
adapted a not very accurately semantic concept, but
acceptable in daily practice. The debate about whether
the MS is just a combination of unrelated phenotypes
still continues.
The tendency to associate cardiovascular risk factors more often than would be expected simply by
chance began to spread more than 80 years ago, when
Kylin described the combination of hypertension,
hyperglycemia, and hyperuricemia, and their connection with cardiovascular risk. (1) The term “metabolic
syndrome” was included during the 1980s, and the
whole concept was boosted after the “Banting” conference, in charge of Gerald Reaven, in 1988, which
was published that year in the journal Diabetes. (2)
This emeritus Professor of Medicine from Stanford
University emphasized the importance of resistance
to insulin as a common denominator of clinical and
metabolical manifestations, like hyperinsulinemia,
glucose intolerance, increased triglycerides, reduced
HDL cholesterol, and hypertension.
This group was called “X syndrome” and suggested
its great relevance as precursor of diabetes and cardiovascular disease.
Since then, there was great scientific interest from
basic, clinical and epidemiological research, which advanced exponentially over time. Conclusive proof of this
is that a bibliographic search of the term “metabolic
syndrome” performed in PubMed in February 2010
showed 29,592 bibliographic citations, almost half of
them published in the last 4 years.
In an interesting study published in the present
issue of the Revista, Paragano et al analyze the impact
MS and its components may have on the arterial wall.
The selected marker of arterial stiffness was the differential pressure or pulse pressure (PP). It is known
that when the arterial wall is affected by disease or
ageing, it modifies its mechanical properties, and thus
becomes less distensible. Therefore, it loses its capacity
of adapting to volume changes caused by the phases of
the cardiac cycle: pressure rises during systolic ejection, and during diastole, it falls to a greater extent
than in normal conditions, and therefore, PP range is
wider. The authors measured the PP in 1,155 apparently healthy individuals of both sexes, and correlated
it (with the corresponding statistic adjustments) with
the presence of MS, and of each component in particular. The association was present for all the variables,
except for the HDL cholesterol, which showed opposite
correlation. (3)
As expressed by the authors, the PP is a surrogate
marker of arterial stiffness, and the use of more direct
indicators –such as the pulse wave velocity (PWV)
comparing carotid and femoral signals– can be more
accurate, since the velocity at which the pulse wave
propagates through the arterial system is a direct
function of wall stiffness. (4) This technique has
been widely used in clinics, and we have used it, for
instance, to evaluate the endothelial function through
post-ischemic hyperflow-mediated vasodilation (5), and
to analyze the effect of antihypertensive agents (angiotensin-converting enzyme inhibitors) on the arterial
elasticity, in addition to its antihypertensive action.
(6) If we agree that one of the basic pathophysiologic
mechanisms that underlie MS is resistance to insulin
and its resulting hyperinsulinemia, it is known that the
latter increases the stiffness of the vessel walls. Hansen
et al –among others– found a direct and independent
connection between the level of insulinemia and the
PWV in a large population survey in Denmark. (7)
The most original and intriguing observation reported by Paragano et al is the paradoxical effect of
HDL cholesterol on the PP (HDL ≤ 40/50 = 44 ± 3 vs
HDL > 40/50 = 47 ± 3; p < 0.001), as described in
Table 3. (3) This finding shows that the rise in HDL
cholesterol increases PP and contradicts other experiences, in which HDL cholesterol is neutral or beneficial
for the mechanical properties of the vessel walls. (8-10)
There is plenty of widely known evidence that relates
the increase in HDL cholesterol with cardiovascular
health: not only does it promote reverse cholesterol
Full Member of the Argentine Society of Cardiology
Associate Professor of Cardiology. University of Buenos Aires
Chief of the Division of Cardiology, Hospital de Clínicas “José de San Martín”.
MTSAC
1
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REVISTA ARGENTINA DE CARDIOLOGÍA / VOL 78 Nº 3 / MAY-JUNe 2010
transport from the peripheral tissues to the liver but
also has antioxidant, antiinflammatory, antithrombotic, and profibrinolytic properties. (11) Nissen et al
demonstrated that increasing HDL cholesterol level
with intravenous administration of recombinant APO
A-1 Milano can cause regression of atheroma plaques
evaluated with intravascular ultrasound. (12) It is
reasonable to accept that normalization of structural
compositon of the wall should result in an improvement of its elastic properties. These pathophysiological
mechanisms have their clinical expression: The analysis of four of the major American prospective studies
showed that for every 1 mg/dl rise in HDL cholesterol,
there is 2-3% reduction of cardiovascular risk. (13) An
analysis on 1,220 consecutive individuals who went
to a cardiology clinic showed that, of the five classic
components of MS, low HDL cholesterol was the one
most strongly associated with a history of ischemic
heart disease. (14)
In conclusion, the work of Paragano et al is an important contribution, and poses a paradox that can be
attributed only to chance or to mechanisms that will
be clarified in future studies.
BIBLIOGRAPHY
1. Kylin E. Studien ubre das hypertonie-hyperglycaemia-hyperurikamiesyndrome. Zentralbaltt fur Innere Medizin 1923; 44:105-27.
2. Reaven GM. Banting lecture 1998. Role of insulin resistance in
human disease. Diabetes 1988; 37:1595-607.
3. Paragano AJ, Machado R, Curotto Grasiosi J, Suárez DH, Cordero
DJ, Alasia D et al. Relación del síndrome metabólico y sus componentes con la presión del pulso en personas sin enfermedad aparente.
Rev Argent Cardiol 2010; 78:215-21.
4. Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac
AM, Target R, et al. Assessment of arterial distensibility by automatic
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5. Rusak EJ, Bellido CA, Iavícoli OR, Vázquez ST, Duarte M, Lerman J.
Assessment of endothelial function by means of flow mediated changes
using pulse wave velocity. J Clin Hypertens (in press).
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pressure decrease after 5 years of antihypertensive treatment. J Clin
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7. Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen
C. Relation between insulin and aortic stiffness: a population based
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10. Choi KM, Lee KW, Seo JA, Oh JH, Kim SG, Kim NH, et al.
Relationship between brachial-ankle pulse wave velocity and cardiovascular risk factors of the metabolic syndrome. Diabetes Res Clin
Pract 2004; 66;57-61.
11. Cutri BA, Hime NJ, Nicholls SJ. High-density lipoproteins: an
emerging target in the prevention of cardiovascular disease. Cell
Research 2006; 16:799-808.
12. Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ,
Yasin M, et al. Effect of recombinant ApoA-I Milano on coronary
atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003; 290:2292-300.
13. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli
WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation
1989; 79:8-15.
14. Lerman J. Epidemiología del síndrome metabólico. In: Lerman J,
Iglesias R, editores. Enfoque integral del síndrome metabólico. 2nd
ed. Buenos Aires: Editorial Intermédica; 2009. p. 18.